The synthesis of anthracycline antitumor antibiotics (adriamycin, daunomycin, etc.) will be investigated using three separate routes. One approach proposes transformation of an anthraquinone derived from protetrone, a fermentation by-product of tetracycline producing microorganisms, into anthracyclinones by electrocyclic ring A formation. The formation of the anthraquinone from other tetracycline fermentation products (tetramide blue, tetramide green) will be attempted as an alternative source of it. A second approach depends on a short, regiospecific total synthesis of the anthraquinone from available substituted benzoic acids. The third approach proposes to prepare optically active anthracyclinones from 6-methylene-5-oxytetracycline by selective synthetic modifications of ring A. New anthracycline analogs will be synthesized by one or more of the three proposed routes, which will contain novel ring C or D modifications. One key target analog will be a C(12) quinone methide. The antitumor activity of new analogs will be determined in vivo and in vitro using cell culture or animal screens. The related anthracycline antibiotics, pyrromycin, cinerubin, and aklavine, will be synthesized by a variant of the protetrone-based route.